Abstract

Introduction: Patients with atrial fibrillation (AF) are at an increased risk of developing dementia, and this risk appears sensitive to quality of warfarin control. Longstanding warfarin use predisposes AF patients to the development of microbleeds if they are over-anticoagulated and microemboli if they are under-anticoagulated. The novel oral anticoagulants (NOACs) offer an alternative to warfarin with a predictable anticoagulant effect, and comparatively favorable intracranial bleeding and thrombosis rates which may lower the risk of dementia. Hypothesis: The use of NOACs will be associated with a lower risk of stroke, TIA, and dementia compared to warfarin. Methods: Patients receiving long-term anticoagulation therapy with either warfarin or a single NOAC for thromboembolism prevention were studied (June 2010-December 2014). NOAC and warfarin patients were matched 1:1 by index date (± 6 months) and propensity score (±0.01). Multivariable Cox hazard regression was performed to evaluate the association of NOAC compared to warfarin use for the composite outcome of dementia, stroke, and TIA. Results: A total of 5,254 (2,627 per group) patients were studied, and those receiving NOACs included: apixaban= 590 (22.5%), dabigatran=583 (22.2%), and rivaroxaban=1,454 (55.3%). Average age was 72.4±10.9 and 59.0% were male. The majority of patients were receiving long-term anticoagulation for AF (warfarin: 96.5% vs. NOAC: 92.7%, p<0.0001). History of a prior stroke/TIA were similar between the groups (warfarin: 10.7% vs. NOAC: 10.8%, p=0.89). Dementia incidence alone was lower in the NOAC group compared to the warfarin group (0.3% vs. 1.6%, p<0.0001). The composite outcome of dementia, stroke, and TIA occurred in 4.7% of warfarin patients and 1.8% of NOAC patients (p<0.0001). After adjustment, patients taking NOACs had a 51% decreased risk of dementia incidence or subsequent stroke or TIA compared to patients taking warfarin (HR=0.49 (0.35, 0.69), p<0.0001). Conclusions: This study shows the use of NOACs in a community setting to be superior to that of warfarin for the composite outcome of dementia, stroke, and TIA among patients receiving long-term oral anticoagulation.

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